Studies in this laboratory have shown that nerve growth factor (NGF) is capable of initiating the classical complement pathway by cleaving zymogen, C4, and C2. This is a function normally mediated by the activated first component of complement, C1. This C1-like activity of NGF can be regulated by the C1 inhibition protein. Recent studies have demonstrated that murine NGF in the presence of human plasma can act as a chemotactic factor for human polymorphonuclear leukocytes in vitro. This activity did not require the known serine esterase activity by NGF. In an in vivo system, NGF injected into the skin of mice caused the local accumulation of polymorphonuclear leukocytes. This activity was absolutely dependent on the enzyme activity of the gamma subunit of NGF. These observations may provide an explanation for the reported ability of NGF to accelerate healing of experimentally induced wounds. (HF)